PROJECT SUMMARY/ABSTRACT BACKGROUND. Genetic testing has a multigenerational impact, as actionable pathogenic variants can identify multiple family members at risk. Currently in the United States, a person at actionable risk through genetic testing is responsible for contacting their own family members and communicating risk. However, incomplete or non-disclosure to relatives is prevalent, and up to a third of at-risk relatives who may have actionable genetic findings go un-notified. Despite preliminary data suggesting that genetic testing patients are open to having their health system directly contact relatives who receive care in the same system to notify them of their potential risk, how such outreach would work in practice is not well understood and represents a critical gap. METHODS. We will conduct a human-centered design and feasibility study of health system-led familial outreach and risk notification. All project activities will be guided by ethical frameworks of learning healthcare systems, clinical care, and public health, as well as by emerging scholarship on relational conceptualizations of autonomy and clinicians' fiduciary obligations to patients and families in genetic services. The first aim will use qualitative human centered design methods to ascertain the needs of patients, their relatives, and clinical and health system stakeholders. We will conduct two rounds of design workshops using future workshop and nominal group techniques with probands and their relatives; and finalize the design with clinician and organizational stakeholders. The product of this aim will be a set of generalizable requirements for use by ours and other health systems engaged in direct outreach to relatives. In the second aim, we will test the outreach process in a limited prospective sample of relatives. We will implement the workflow designed in Aim 1 with a prospective cohort of health system members receiving actionable results from testing for BRCA1/2 or Lynch syndrome. We will identify each consenting proband's genetic relatives who are members of the same health system. Consenting relatives will be randomly assigned to either the outreach process designed in Aim 1, or to no further outreach. We will use the proband as the unit of randomization to allow for clustering within family, and stratify randomization on BRCA or Lynch testing. OUTCOME ASSESSMENT. Using a combination of in-depth cognitive interviews and survey, feasibility outcomes assessed will include acceptability of the process, satisfaction with care and with treatment/testing decisions, impact of direct outreach on family communications, actions taken after notification, and any unintended consequences. We will assess limited efficacy of direct outreach in increasing use of genetic counseling and testing in relatives who received direct outreach compared to those who did not at 6-8 weeks.